Over the past 6 years, the PIs have worked together at the Ohio State University (OSU) to build a translational research program in the orphan disease thrombotic TTP. Approximately three years ago, these PIs initiated a Phase 3 clinical trial with an internal pilot study entitled "A Multi-Center, Randomized Study of CSA or Corticosteroids as an Adjunct to PE in Initial Therapy of TTP." Through the internal pilot portion of the study, the PIs have enrolled eleven subjects from OSU and one subject from another participating site, and collected and analyzed all corresponding clinical and laboratory data. The PIs are requesting funding through this grant program to provide the necessary resources to enroll sufficient subjects from multiple centers in order to bring about successful completion of this trial in a rare disease. In this proposal, a total of 6 clinical sites will enroll a total of 72 study subjects to determine if CSA given individually as an adjunct to PE increases the treatment success rate (clinical response and free from exacerbation for 30 days post-PE) in patients with TTP compared to those patients given corticosteroids as an adjunct to PE. In addition to the primary goal and corresponding endpoint, the PIs will also evaluate multiple secondary endpoints that can help to elucidate the molecular mechanisms and safety for each of these treatment interventions. These include comparison of the CSA + PE treatment arm versus the corticosteroid + PE treatment arm with respect to: 1) Exacerbation rate within 30 days post-PE;2) Clinical response rate;3) Number of exchange procedures to achieve clinical response;4) Relapse rate (recurrent disease >30 days after last PE);and 5) Safety data for CSA as an adjunct to PE.